Viral myocarditis and dilated cardiomyopathy: Etiology and pathogenesis

Current Pharmaceutical Design

Volumn 22, Issue 4, 2016, Pages 408-426

  Huber, Sally A ^a  

^a UNIVERSITY OF VERMONT   (United States)

Author keywords

Autoimmunity; Dilated cardiomyopathy; Endothelial mesenchymal transition; Fibrosis; Immunosuppression; Myocarditis; Persistent infection; Picornaviruses

Indexed keywords

BETA INTERFERON; CYCLOPHOSPHAMIDE; CYCLOSPORIN A;

ADAPTIVE IMMUNITY; ARTICLE; AUTOIMMUNITY; CONGESTIVE CARDIOMYOPATHY; EOSINOPHIL; FIBROSIS; GIANT CELL; HUMAN; INFECTION; INFLAMMATION; INNATE IMMUNITY; LYMPHOCYTE; MYOCARDITIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; SEX DIFFERENCE; VIRUS MYOCARDITIS; ANIMAL; CARDIOMYOPATHY, DILATED; IMMUNOLOGY; VIROLOGY; VIRUS DISEASES;

ANIMALS; CARDIOMYOPATHY, DILATED; HUMANS; IMMUNITY, INNATE; MYOCARDITIS; VIRUS DISEASES;

EID: 84959323986     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612822666151222160500     Document Type: Article

References (349)

1. Sagar S, Liu PP, Cooper LT, Jr. Myocarditis. Lancet 2012; 379: 738-47.
2. Andreoletti L, Leveque N, Boulagnon C, et al. Viral causes of human myocarditis. Arch Cardiovasc Dis 2009; 102: 559-68.
3. Schultz JC, Hilliard AA, Cooper LT, Jr., Rihal CS. Diagnosis and treatment of viral myocarditis. Mayo Clin Proc 2009; 84: 1001-9.
4. Kawai C, Matsumori A. Dilated cardiomyopathy update: infectious-immune theory revisited. Heart Failure Rev 2013; 18: 703-14.
5. Chapman NM, Kim KS. Persistent coxsackievirus infection: enterovirus persistence in chronic myocarditis and dilated cardiomyopathy. Curr Top Microbiol Immunol 2008; 323: 275-92.
6. Hauck AJ, Kearney DL, Edwards WD. Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error. Mayo Clin Proc 1989; 64: 1235-45.
7. Woodruff J. Viral myocarditis. Am J Pathol 1980; 101: 425-83.
8. Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 2003; 42: 466-72.
9. Kuhl U, Pauschinger M, Noutsias M, et al. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction. Circulation 2005; 111: 887-93.
10. Bocchi EA, Arias A, Verdejo H, et al. The reality of heart failure in Latin America. J Am Coll Cardiol 2013; 62: 949-58.
11. Stohr K, Bucher D, Colgate T, Wood J. Influenza virus surveillance, vaccine strain selection, and manufacture. Methods Mol Biol 2012; 865: 147-62.
12. Linder JE, Kraft DC, Mohamed Y, et al. Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades. J Allergy Clin Immunol 2013; 131: 69-77 e61-66.
13. Jin Y, Zhang RF, Xie ZP, et al. Prevalence of adenovirus inchildren with acute respiratory tract infection in Lanzhou, China. Virol J 2013; 10: 271.
14. Solomon T, Lewthwaite P, Perera D, et al. Virology, epidemiology,pathogenesis, and control of enterovirus 71. Lancet Infect Dis 2010; 10: 778-90.
15. Chang LY, Chang IS, Chen WJ, et al. HLA-A33 is associated withsusceptibility to enterovirus 71 infection. Pediatrics 2008; 122: 1271-6.
16. Gladkova ND, Vostokova AA, Zvereva KV, et al. The HLAsystem and Coxsackie B viral myocarditis in adults. Kardiologiia 1986; 26: 24-8.
17. Leone O, Veinot JP, Angelini A, et al. 2011 consensus statementon endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology. Cardiovasc Pathol 2012; 21: 245-74.
18. Basso C, Calabrese F, Angelini A, et al. Classification andhistological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease. Heart Fail Rev 2013; 18: 673-81.
19. Sujino Y, Kimura F, Tanno J, et al. Cardiac magnetic resonanceimaging in giant cell myocarditis: intriguing associations with clinical and pathological features. Circulation 2014; 129: e467-e9.
20. Seguela PE, Iriart X, Acar P, et al. Eosinophilic cardiac disease:Molecular, clinical and imaging aspects. Arch Cardiovasc Dis 2015; 108: 258-68.
21. Ginsberg F, Parrillo JE. Eosinophilic myocarditis. Heart Fail Clin2005; 1: 419-29.
22. Eicher JC, Bonnotte B, L'Huillier I, et al. Cardiovascularmanifestations of eosinophilia: clinical and echocardiographic presentation. Rev Med Interne 2009; 30: 1011-9.
23. Aslan I, Fischer M, Laser KT, Haas NA. Eosinophilic myocarditisin an adolescent: a case report and review of the literature. Cardiol Young 2012: 1-7.
24. Yanagisawa T, Inomata T, Watanabe I, et al. Clinical significanceof corticosteroid therapy for eosinophilic myocarditis. Int Heart J 2011; 52: 110-3.
25. Blauwet LA, Cooper LT. Idiopathic giant cell myocarditis andcardiac sarcoidosis. Heart Fail Rev 2013; 18(6): 733-46.
26. Bernstein M, Konzelmann F, Sidlick D. Boeck's Sarcoid: report ofa case with visceral involvement. Ann Int Med 1929; 44: 721-34.
27. Tesluk H. Giant cell versus granulomatous myocarditis. Am J ClinPathol 1956; 26: 1326-33.
28. Whitehead R. Isolated Myocarditis. Br Heart J 1965; 27: 220-30.
29. Okada R, Wakafuji S. Myocarditis in autopsy. Heart Vessels Suppl 1985; 1: 23-9.
30. Drut RM, Drut R. Giant-cell myocarditis in a newborn withcongenital herpes simplex virus (HSV) infection: an immunohistochemical study on the origin of the giant cells. Pediatr Pathol 1986; 6: 431-7.
31. Meyer T, Grumbach IM, Kreuzer H, Morguet AJ. Giant cellmyocarditis due to coxsackie B2 virus infection. Cardiology 1997; 88: 296-9.
32. Dennert R, Schalla S, Suylen RJ, et al. Giant cell myocarditistriggered by a parvovirus B19 infection. Int J Cardiol 2009; 134: 115-6.
33. Mascaro-Blanco A, Alvarez K, Yu X, et al. Consequences ofunlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies. Autoimmunity 2008; 41: 442-53.
34. Cooper LT, Jr., Berry GJ, Shabetai R. Idiopathic giant-cellmyocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Eng J Med 1997; 336: 1860-6.
35. Cooper LT, Jr. Giant cell myocarditis: diagnosis and treatment.Herz 2000; 25: 291-8.
36. Cooper LT, Jr., ElAmm C. Giant cell myocarditis. Diagnosis andtreatment. Herz 2012; 37: 632-6.
37. Baughman RP, Lower EE, du Bois RM. Sarcoidosis. Lancet 2003;361: 1111-8.
38. Eishi Y, Suga M, Ishige I, et al. Quantitative analysis ofmycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol 2002; 40: 198-204.
39. Benzagmout M, Oudghiri B, Boujraf S, et al. Fatalneurosarcoidosis induced by interferon alpha treatment in chronic hepatitis C. Neurol India 2010; 58: 949-50.
40. Ramos-Casals M, Munoz S, Medina F, et al. Systemic autoimmunediseases in patients with hepatitis C virus infection: characterization of 1020 cases (The HISPAMEC Registry). J Rheumatol 2009; 36: 1442-8.
41. Iwai K, Sekiguti M, Hosoda Y, et al. Racial difference in cardiacsarcoidosis incidence observed at autopsy. Sarcoidosis 1994; 11: 26-31.
42. Kim DS. Sarcoidosis in Korea: report of the Second NationwideSurvey. Sarcoidosis Vasc Diffuse Lung Dis 2001; 18: 176-80.
43. Roberts WC, McAllister HA, Jr., Ferrans VJ. Sarcoidosis of theheart. A clinicopathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 11). Am J Med 1977; 63: 86-108.
44. Judson MA, Baughman RP, Teirstein AS, et al. Defining organinvolvement in sarcoidosis: the ACCESS proposed instrumentACCESS research group. a case control etiologic study of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 1999; 16: 75-86.
45. Yazaki Y, Isobe M, Hiroe M, et al. Prognostic determinants oflong-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J Cardiol 2001; 88: 1006-10.
46. Deng JC, Baughman RP, Lynch JP, 3rd. Cardiac involvement insarcoidosis. Semin Respir Crit Care Med 2002; 23: 513-27.
47. Huang CT, Heurich AE, Sutton AL, Lyons HA. Mortality insarcoidosis. A changing pattern of the causes of death. Eur J Respir Dis 1981; 62: 231-8.
48. Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: aclinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 1978; 58: 1204-11.
49. Takashige N, Naruse TK, Matsumori A, et al. Geneticpolymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis. Tissue Antigens 1999; 54: 191-3.
50. Naruse TK, Matsuzawa Y, Ota M, et al. HLA-DQB1*0601 isprimarily associated with the susceptibility to cardiac sarcoidosis. Tissue Antigens 2000; 56: 52-7.
51. Dubrey SW, Sharma R, Underwood R, Mittal T. Cardiacsarcoidosis: diagnosis and management. Postgraduate Med J 2015; 91: 384-94.
52. Lieberman EB, Hutchins GM, Herskowitz A, et al.Clinicopathologic description of myocarditis. J Am Coll Cardiol 1991; 18: 1617-26.
53. McCarthy RE, 3rd, Boehmer JP, Hruban RH, et al. Long-termoutcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med 2000; 342: 690-5.
54. Mendes LA, Picard MH, Dec GW, et al. Ventricular remodeling inactive myocarditis. Myocarditis Treatment Trial. Am Heart J 1999; 138: 303-8.
55. Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis. JAm Coll Cardiol 2012; 59: 779-92.
56. Cooper LT, Jr., Keren A, Sliwa K, et al. The global burden ofmyocarditis: part 1: a systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study. Glob Heart 2014; 9: 121-9.
57. Fairweather D, Petri MA, Coronado MJ, Cooper LT. Autoimmuneheart disease: role of sex hormones and autoantibodies in disease pathogenesis. Exp Rev Clin Immunol 2012; 8: 269-84.
58. Chandra N, Bastiaenen R, Papadakis M, Sharma S. Sudden cardiacdeath in young athletes: practical challenges and diagnostic dilemmas. J Am Coll Cardiol 2013; 61: 1027-40.
59. Arrigan MT, Killeen RP, Dodd JD, Torreggiani WC. Imagingspectrum of sudden athlete cardiac death. Clin Radiol 2011; 66: 203-23.
60. Theleman KP, Kuiper JJ, Roberts WC. Acute myocarditis(predominately lymphocytic) causing sudden death without heart failure. Am J Cardiol 2001; 88: 1078-83.
61. Caforio AL, Marcolongo R, Jahns R, et al. Immune-mediated andautoimmune myocarditis: clinical presentation, diagnosis and management. Heart Fail Rev 2013; 18: 715-32.
62. Richardson P, McKenna W, Bristow M, et al. Report of the 1995world health organization/international society and federation of cardiology task force on the definition and classification of cardiomyopathies. Circulation 1996; 93: 841-2.
63. Cooper Jr. L, Knowlton K. Myocarditis. In: Braunwald's HeartDisease: A Textbook of Cardiovascular Medicine. 10th ed. DL M, Zipes D, Libby P, Bonow R, Eds. USA: Elsevier Inc 2014.
64. Mason J, al e. A clinical trial of immunosuppressive therapy formyocarditis. The myocarditis treatment trial investigators. N Engl J Med 1995; 333: 269-75.
65. Kuhl U, Pauschinger M, Schwimmbeck PL, et al. Interferon-betatreatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction. Circulation 2003; 107: 2793-8.
66. Prud'homme GJ, Parfrey NA, Vanier LE. Cyclosporine-inducedautoimmunity and immune hyperreactivity. Autoimmunity 1991; 9: 345-56.
67. Estrin M, Smith C, Huber S. Coxsackievirus B-3 myocarditis. T-cell autoimmunity to heart antigens is resistant to cyclosporin-A treatment. Am J Pathol 1986; 125: 244-51.
68. Drucker NA, Colan SD, Lewis AB, et al. Gamma-globulintreatment of acute myocarditis in the pediatric population. Circulation 1994; 89: 252-7.
69. Kishimoto C, Takada H, Hiraoka Y. Intravenous IgG: supertherapyfor myocarditis and acute dilated cardiomyopathy. Circulation 1999; 99: 975.
70. Tedeschi A, Airaghi L, Giannini S, et al. High-dose intravenousimmunoglobulin in the treatment of acute myocarditis. A case report and review of the literature. J Int Med 2002; 251: 169-73.
71. McNamara DM, Holubkov R, Starling RC, et al. Controlled trial ofintravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001; 103: 2254-9.
72. Basso C, Burke M, Fornes P, et al. Guidelines for autopsyinvestigation of sudden cardiac death. Virchows Arch 2008; 452: 11-8.
73. Fairweather D, Cooper LT, Jr., Blauwet LA. Sex and genderdifferences in myocarditis and dilated cardiomyopathy. Curr Probl Cardiol 2013; 38: 7-46.
74. Lee LV, Foody JM. Women and heart disease. Cardiol Clin 2011;29: 35-45.
75. McNamara DM, Starling RC, Cooper LT, et al. Clinical anddemographic predictors of outcomes in recent onset dilated cardiomyopathy: results of the IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 study. J Am Coll Cardiol 2011; 58: 1112-8.
76. Regitz-Zagrosek V, Seeland U. Sex and gender differences inmyocardial hypertrophy and heart failure. Wien Med Wochenschr 2011; 161: 109-16.
77. Roger VL, Go AS, Lloyd-Jones DM, et al. Executive summary:heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 2012; 125: 188-97.
78. Ludden TE, Edwards JE. Carditis in poliomyelitis; an anatomicstudy of 35 cases and review of the literature. Am J Pathol 1949; 25: 357-81.
79. Sainani GS, Krompotic E, Slodki SJ. Adult heart disease due to theCoxsackie virus B infection. Medicine (Baltimore) 1968; 47: 133-47.
80. Caforio AL, Calabrese F, Angelini A, et al. A prospective study ofbiopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 2007; 28: 1326-33.
81. Magnani JW, Danik HJ, Dec GW, Jr., DiSalvo TG. Survival inbiopsy-proven myocarditis: a long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors. Am Heart J 2006; 151: 463-70.
82. Gillum RF. Idiopathic cardiomyopathy in the United States, 1970-1982. Am Heart J 1986; 111: 752-5.
83. Frisancho-Kiss S, Coronado MJ, Frisancho JA, et al. Gonadectomyof male BALB/c mice increases Tim-3(+) alternatively activated M2 macrophages, Tim-3(+) T cells, Th2 cells and Treg in the heart during acute coxsackievirus-induced myocarditis. Brain Behav Immun 2009; 23: 649-57.
84. Huber SA, Job LP, Auld KR. Influence of sex hormones onCoxsackie B-3 virus infection in Balb/c mice. Cell Immunol 1982; 67: 173-9.
85. Klein SL. The effects of hormones on sex differences in infection:from genes to behavior. Neurosci Biobehav Rev 2000; 24: 627-38.
86. Klein SL, Huber SA. Sex Differences in Susceptibility to ViralInfection. In: Klein SL, Roberts CW, Eds. Sex Hormones and Immunity to Infection. Berlin, Germany: Springer Verlag 2010.
87. Jordan GW, Bolton V. Interferon-sensitive coxsackievirus variantsin nature. J Interferon Res 1985; 5: 289-96.
88. Qashqari H, Al-Mars A, Chaudhary A, et al. Understanding themolecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance. Infection, genetics and evolution. J Mol Epidemiol Evol Genet Infect Dis 2013; 19: 113-9.
89. Cox JE, McClure LV, Goga A, Sullivan CS. Pan-viral-microRNAscreening identifies interferon inhibition as a common function of diverse viruses. Proc Natl Acad Sci USA 2015; 112: 1856-61.
90. Kabelitz D, Medzhitov R. Innate immunity--cross-talk withadaptive immunity through pattern recognition receptors and cytokines. Curr Opin Immunol 2007; 19: 1-3.
91. Yoneyama M, Onomoto K, Jogi M, et al. Viral RNA detection byRIG-I-like receptors. Curr Opin Immunol 2015; 32: 48-53.
92. Brown J, Wang H, Hajishengallis GN, Martin M. TLR-signalingnetworks: an integration of adaptor molecules, kinases, and cross- talk. J Dent Res 2010; 90: 417-27.
93. Lupfer C, Kanneganti TD. The expanding role of NLRs in antiviralimmunity. Immunol Rev 2013; 255: 13-24.
94. Buskiewicz IA, Koenig A, Huber SA, Budd RC. Caspase-8 andFLIP regulate RIG-I/MDA5-induced innate immune host responses to picornaviruses. Future Virol 2012; 7: 1221-36.
95. Melchjorsen J, Jensen SB, Malmgaard L, et al. Activation of innatedefense against a paramyxovirus is mediated by RIG-I and TLR7 and TLR8 in a cell-type-specific manner. J Virol 2005; 79: 12944-51.
96. Triantafilou K, Orthopoulos G, Vakakis E, et al. Human cardiacinflammatory responses triggered by Coxsackie B viruses are mainly Toll-like receptor (TLR) 8-dependent. Cell Microbiol 2005; 7: 1117-26.
97. Berghofer B, Frommer T, Haley G, et al. TLR7 ligands inducehigher IFN-alpha production in females. J Immunol 2006; 177: 2088-96.
98. Le May C, Chu K, Hu M, et al. Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Proc Natl Acad Sci USA 2006; 103: 9232-7.
99. Huber SA, Kupperman J, Newell MK. Estradiol prevents andtestosterone promotes Fas-dependent apoptosis in CD4+ Th2 cells by altering Bcl 2 expression. Lupus 1999; 8: 384-7.
100. Sheppard R, Bedi M, Kubota T, et al. Myocardial expression of fasand recovery of left ventricular function in patients with recent- onset cardiomyopathy. J Am Coll Cardiol 2005; 46: 1036-42.
101. Ho KK, Anderson KM, Kannel WB, et al. Survival after the onsetof congestive heart failure in Framingham Heart Study subjects. Circulation 1993; 88: 107-15.
102. Fairweather D, Stafford KA, Sung YK. Update on coxsackievirusB3 myocarditis. Curr Opin Rheumatol 2012; 24: 401-7.
103. Lyden D, Olszewski J, Feran M, et al. Coxsackievirus B3-inducedmyocarditis. Effects of sex steroids on viremia and infectivity of cardiocytes. Am J Pathol 1987; 126: 432-8.
104. Huber S, Pfaeffle B. Differential Th1 and Th2 cell responses inmale and female BALB/c mice infected with Coxsackievirus Group B Type 3. J Virol 1994; 68: 5126-32.
105. Cheung PK, Yuan J, Zhang HM, et al. Specific interactions ofmouse organ proteins with the 5'untranslated region of coxsackievirus B3: potential determinants of viral tissue tropism. J Med Virol 2005; 77: 414-24.
106. Huber SA, Haisch C, Lodge PA. Functional diversity in vascularendothelial cells: role in coxsackievirus tropism. J Virol 1990; 64: 4516-22.
107. Klingel K, Rieger P, Mall G, et al. Visualization of enteroviralreplication in myocardial tissue by ultrastructural in situ hybridization: identification of target cells and cytopathic effects. Lab Invest 1998; 78: 1227-37.
108. Dumas F, Preira P, Salome L. Membrane organization of virus andtarget cell plays a role in HIV entry. Biochimie 2014; 107 Pt A: 22-7.
109. Martino TA, Petric M, Weingartl H, et al. The coxsackie-adenovirus receptor (CAR) is used by reference strains and clinical isolates representing all six serotypes of coxsackievirus group B and by swine vesicular disease virus. Virology 2000; 271: 99-108.
110. Wang X, Bergelson JM. Coxsackievirus and adenovirus receptorcytoplasmic and transmembrane domains are not essential for coxsackievirus and adenovirus infection. J Virol 1999; 73: 2559-62.
111. Lin F, Fukuoka Y, Spicer A, et al. Tissue distribution of productsof the mouse decay-accelerating factor (DAF) genes. Exploitation of a Daf1 knock-out mouse and site-specific monoclonal antibodies. Immunology 2001; 104: 215-25.
112. Bazzoni G. Endothelial tight junctions: permeable barriers of thevessel wall. Thrombosis Haemostasis 2006; 95: 36-42.
113. Carson SD, Chapman NM. Coxsackievirus and adenovirus receptor(CAR) binds immunoglobulins. Biochemistry 2001; 40: 14324-9.
114. Coyne CB, Bergelson JM. Virus-induced Abl and Fyn kinasesignals permit coxsackievirus entry through epithelial tight junctions. Cell 2006; 124: 119-31.
115. Ozaki H, Ishii K, Horiuchi H, et al. Cutting edge: combinedtreatment of TNF-alpha and IFN-gamma causes redistribution of junctional adhesion molecule in human endothelial cells. J Immunol 1999; 163: 553-7.
116. Poller W, Fechner H, Noutsias M, et al. Highly variable expressionof virus receptors in the human cardiovascular system. Implications for cardiotropic viral infections and gene therapy. Z Kardiol 2002; 91: 978-91
117. Sharma P, Kolawole AO, Core SB, et al. Sidestream smokeexposure increases the susceptibility of airway epithelia to adenoviral infection. PLoS One 2012; 7: e49930.
118. Rayasam GV, Tulasi VK, Sodhi R, et al. Glycogen synthase kinase3: more than a namesake. Br J Pharmacol 2009; 156: 885-98.
119. Kim L, Kimmel AR. GSK3 at the edge: regulation ofdevelopmental specification and cell polarization. Curr Drug Targets 2006; 7: 1411-9.
120. Vincent T, Neve EP, Johnson JR, et al. A SNAIL1-SMAD3/4transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat Cell Biol 2009; 11: 943-50.
121. Drescher KM, Tracy SM. The CVB and etiology of type 1 diabetes.Curr Top Microbiol Immunol 2008; 323: 259-74.
122. Jubelt B, Lipton HL. Enterovirus/picornavirus infections. HandbClin Neurol 2014; 123: 379-416.
123. Ramsingh AI. CVB-induced pancreatitis and alterations in geneexpression. Curr Top Microbiol Immunol 2008; 323: 241-58.
124. Zautner AE, Jahn B, Hammerschmidt E, et al. N- and 6-O-sulfatedheparan sulfates mediate internalization of coxsackievirus B3 variant PD into CHO-K1 cells. J Virol 2006; 80: 6629-36.
125. Nagy PD, Pogany J. The dependence of viral RNA replication onco-opted host factors. Nat Rev Microbiol 2012; 10: 137-49.
126. Gauntt C, Huber S. Coxsackievirus experimental heart diseases.Front Biosci 2003; 8: e23-e35.
127. Dunn JJ, Bradrick SS, Chapman NM, et al. The stem loop II withinthe 5' nontranslated region of clinical coxsackievirus B3 genomes determines cardiovirulence phenotype in a murine model. J Infect Dis 2003; 187: 1552-61.
128. Melchers WJ, Hoenderop JG, Bruins Slot HJ, et al. Kissing of thetwo predominant hairpin loops in the coxsackie B virus 3' untranslated region is the essential structural feature of the origin of replication required for negative-strand RNA synthesis. J Virol 1997; 71: 686-96.
129. Sean P, Semler BL. Coxsackievirus B RNA replication: lessonsfrom poliovirus. Curr Top Microbiol Immunol 2008; 323: 89-121.
130. Belov GA, Ehrenfeld E. Involvement of cellular membrane trafficproteins in poliovirus replication. Cell Cycle 2007; 6: 36-38.
131. Jackson WT, Giddings TH, Jr., Taylor MP, et al. Subversion ofcellular autophagosomal machinery by RNA viruses. PLoS Biol 2005; 3: e156.
132. Kemball CC, Alirezaei M, Flynn CT, et al. Coxsackievirusinfection induces autophagy-like vesicles and megaphagosomes in pancreatic acinar cells in vivo. J Virol 2010; 84: 12110-24.
133. Cornell CT, Brunner JE, Semler BL. Differential rescue ofpoliovirus RNA replication functions by genetically modified RNA polymerase precursors. J Virol 2004; 78: 13007-18.
134. Rueckert R. Picronaviruses. Fundamental Virology. 3rd ed. In:Fields BN, Knipe DM, Howley RM, et al. Eds. Philadelphia, PA: Lippincott-Raven 1996; pp. 477-522.
135. Kerekatte V, Keiper BD, Badorff C, et al. Cleavage of Poly(A)-binding protein by coxsackievirus 2A protease in vitro and in vivo: another mechanism for host protein synthesis shutoff? J Virol 1999; 73: 709-17.
136. Feuer R, Mena I, Pagarigan R, et al. Cell cycle status affectscoxsackievirus replication, persistence, and reactivation in vitro. J Virol 2002; 76: 4430-40.
137. Feuer R, Mena I, Pagarigan RR, et al. Coxsackievirus replicationand the cell cycle: a potential regulatory mechanism for viral persistence/latency. Med Microbiol Immunol (Berl) 2003.
138. Kandolf R, Sauter M, Aepinus C, et al. Mechanisms andconsequences of enterovirus persistence in cardiac myocytes and cells of the immune system. Virus Res 1999; 62: 149-58.
139. Chapman NM, Kim KS, Drescher KM, et al. 5' terminal deletionsin the genome of a coxsackievirus B2 strain occurred naturally in human heart. Virology 2008; 375: 480-91.
140. Kim KS, Chapman NM, Tracy S. Replication of coxsackievirus B3in primary cell cultures generates novel viral genome deletions. J Virol 2008; 82: 2033-7.
141. Chehadeh W, Kerr-Conte J, Pattou F, et al. Persistent infection ofhuman pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in beta cells. J Virol 2000; 74: 10153-64.
142. Schmidtke M, Selinka H, Heim A, et al. Attachment ofcoxsackievirus B3 variants to various cell lines: mapping of phenotypic differences to capsid protein VP1. Virology 2000; 275: 77-88.422
143. Schmidtke M, Merkle I, Klingel K, et al. The viral geneticbackground determines the outcome of coxsackievirus B3 infection in outbred NMRI mice. J Med Virol 2007; 79: 1334-42.
144. Yajima T, Knowlton KU. Viral myocarditis: from the perspectiveof the virus. Circulation 2009; 119: 2615-24.
145. Nugent CI, Johnson KL, Sarnow P, Kirkegaard K. Functionalcoupling between replication and packaging of poliovirus replicon RNA. J Virol 1999; 73: 427-35.
146. Wessely R, Klingel K, Santana LF, et al. Transgenic expression ofreplication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy. J Clin Invest 1998; 102: 1444-53.
147. Badorff C, Lee GH, Knowlton KU. Enteroviral cardiomyopathy:bad news for the dystrophin-glycoprotein complex. Herz 2000; 25: 227-32.
148. Badorff C, Lee GH, Lamphear BJ, et al. Enteroviral protease 2Acleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med 1999; 5: 320-6.
149. Lim BK, Peter AK, Xiong D, et al. Inhibition of Coxsackievirus-associated dystrophin cleavage prevents cardiomyopathy. J Clin Invest 2013; 123: 5146-51.
150. Liu P, Aitken K, Kong YY, et al. The tyrosine kinase p56lck isessential in coxsackievirus B3-mediated heart disease. Nat Med 2000; 6: 429-34.
151. Huber SA, Rincon M. Coxsackievirus B3 induction of NFAT:requirement for myocarditis susceptibility. Virology 2008; 381: 155-60.
152. Hermann-Kleiter N, Baier G. NFAT pulls the strings during CD4+T helper cell effector functions. Blood 2010; 115: 2989-97.
153. Kubarek L, Jagodzinski PP. Epigenetic up-regulation of CXCR4and CXCL12 expression by 17 beta-estradiol and tamoxifen is associated with formation of DNA methyltransferase 3B4 splice variant in Ishikawa endometrial adenocarcinoma cells. FEBS Lett 2007; 581: 1441-8.
154. Mo R, Chen J, Grolleau-Julius A, et al. Estrogen regulates CCRgene expression and function in T lymphocytes. J Immunol 2005; 174: 6023-9.
155. Gavrilovskaya IN, Shepley M, Shaw R, et al. beta3 Integrinsmediate the cellular entry of hantaviruses that cause respiratory failure. Proc Natl Acad Sci USA 1998; 95: 7074-9.
156. Roivainen M, Piirainen L, Hovi T, et al. Entry of coxsackievirusA9 into host cells: specific interactions with alpha v beta 3 integrin, the vitronectin receptor. Virology 1994; 203: 357-365.
157. Wickham TJ, Filardo EJ, Cheresh DA, Nemerow GR. Integrinalpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization. J Cell Biol 1994; 127: 257-64.
158. Wickham TJ, Mathias P, Cheresh DA, Nemerow GR. Integrinsalpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 1993; 73: 309-19.
159. Li CF, Ross FP, Cao X, Teitelbaum SL. Estrogen enhances alpha vbeta 3 integrin expression by avian osteoclast precursors via stabilization of beta 3 integrin mRNA. Mol Endocrinol Baltimore Md 1995; 9: 805-13.
160. Woodward TL, Mienaltowski AS, Modi RR, et al. Fibronectin andthe alpha(5)beta(1) integrin are under developmental and ovarian steroid regulation in the normal mouse mammary gland. Endocrinology 2001; 142: 3214-22.
161. Song WC, Deng C, Raszmann K, et al. Mouse decay-acceleratingfactor: selective and tissue-specific induction by estrogen of the gene encoding the glycosylphosphatidylinositol-anchored form. J Immunol 1996; 157: 4166-72.
162. Sartini D, Moussawi M, Sallam R, et al. Correlation between serumestradiol in the follicular phase of the ovarian cycle and decay acceleration factor (DAF) expression on red blood cells and coxsackiervirus B-3 induced hemagglutination in young cycling women. Am J Reprod Immunol 2004; 51: 180-7.
163. Kemball CC, Alirezaei M, Whitton JL. Type B coxsackievirusesand their interactions with the innate and adaptive immune systems. Future Microbiol 2010; 5: 1329-47.
164. Buskiewicz IA, Huber SA. MDA5: the almighty for Myocardium.Circulation. Heart failure 2013; 6: 153-5.
165. Zarember KA, Godowski PJ. Tissue expression of human Toll-likereceptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol 2002; 168: 554-61.
166. Netea MG, Van der Meer JW, Sutmuller RP, et al. From theTh1/Th2 paradigm towards a Toll-like receptor/T-helper bias. Antimicrobial Agents Chemother 2005; 49: 3991-6.
167. Frisancho-Kiss S, Davis SE, Nyland JF, et al. Cutting edge: cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease. J Immunol 2007; 178: 6710-4.
168. Abston ED, Coronado MJ, Bucek A, et al. TLR3 deficiencyinduces chronic inflammatory cardiomyopathy in resistant mice following coxsackievirus B3 infection: role for IL-4. Am J Physiol Regul Integr Comp Physiol 2013; 304: R267-77.
169. Fairweather D, Frisancho-Kiss S, Rose NR. Viruses as adjuvantsfor autoimmunity: evidence from Coxsackievirus-induced myocarditis. Rev Med Virol 2005; 15: 17-27.
170. Roberts BJ, Dragon JA, Moussawi M, Huber SA. Sex-specificsignaling through Toll-Like Receptors 2 and 4 contributes to survival outcome of Coxsackievirus B3 infection in C57Bl/6 mice. Biol Sex Differ 2012; 3: 25.
171. Roberts BJ, Moussawi M, Huber SA. Sex differences in TLR2 andTLR4 expression and their effect on coxsackievirus-induced autoimmune myocarditis. Exp Mol Pathol 2013; 94: 58-64.
172. Zhang P, Cox CJ, Alvarez KM, Cunningham MW. Cutting edge:cardiac myosin activates innate immune responses through TLRs. J Immunol 2009; 183: 27-31.
173. Huber S. Heat-shock protein induction in adriamycin andpicornavirus-infected cardiocytes. Lab Invest 1992; 67: 218-24.
174. de Jong PR, Schadenberg AW, Jansen NJ, Prakken BJ. Hsp70 andcardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects. Cell Stress Chaperones 2009; 14: 117-31.
175. Gorbea C, Makar KA, Pauschinger M, et al. A role for Toll-likereceptor 3 variants in host susceptibility to enteroviral myocarditis and dilated cardiomyopathy. J Biol Chem 2010; 285: 23208-23.
176. Wang JP, Cerny A, Asher DR, et al. MDA5 and MAVS mediatetype I interferon responses to coxsackie B virus. J Virol 2010; 84: 254-60.
177. Sozzani S, Bosisio D, Scarsi M, Tincani A. Type I interferons insystemic autoimmunity. Autoimmunity 2010; 43: 196-203.
178. Crampton SP, Deane JA, Feigenbaum L, Bolland S. Ifih1 genedose effect reveals MDA5-mediated chronic type I IFN gene signature, viral resistance, and accelerated autoimmunity. J Immunol 2012; 188: 1451-9.
179. Rice GI, del Toro Duany Y, Jenkinson EM, et al. Gain-of-functionmutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet 2014; 46: 503-9.
180. Biron CA, Nguyen KB, Pien GC, et al. Natural killer cells inantiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 1999; 17: 189-220.
181. Vossen MT, Westerhout EM, Soderberg-Naucler C, Wiertz EJ.Viral immune evasion: a masterpiece of evolution. Immunogenetics 2002; 54: 527-42.
182. Moretta L, Moretta A. Unravelling natural killer cell function:triggering and inhibitory human NK receptors. EMBO J 2004; 23: 255-9.
183. Moretta L, Moretta A. Killer immunoglobulin-like receptors. CurrOpin Immunol 2004; 16: 626-33.
184. Gauntt C, Godney E, Lutton C. Host factors regulating viralclearance. Pathol Immunopathol Res 1988; 7: 251-65.
185. Gauntt C, Godney E, Lutton C, Fernandes G. Role of natural killercells in experimental murine myocarditis. Springer Semin Immunopathol 1989; 11: 51-9.
186. Vella C, Festenstein H. Coxsackievirus B4 infection of the mousepancreas: the role of natural killer cells in the control of virus replication and resistance to infection. J Gen Virol 1992; 73 (Pt 6): 1379-86.
187. Chow LH, Ye Y, Linder J, McManus BM. Phenotypic analysis ofinfiltrating cells in human myocarditis. An immunohistochemical study in paraffin-embedded tissue. Arch Pathol Lab Med 1989; 113: 1357-62.
188. Maisch B, Schonian U, Crombach M, et al. Cytomegalovirusassociated inflammatory heart muscle disease. Scandinavian journal of infectious diseases. Supplementum 1993; 88: 135-48.
189. Yang YZ, Jin PY, Guo Q, et al. Effect of Astragulasmembranaceus on natural killer cell activity and induction of alpha-Viral Myocarditis and Dilated Cardiomyopathy: Etiology and Pathogenesisand gamma-interferon in patients with Coxsackie B viral myocarditis. Chinese Med J 1990; 103: 304-7.
190. Zingoni A, Sornasse T, Cocks BG, et al. NK cell regulation of Tcell-mediated responses. Mol Immunol 2005; 42: 451-4.
191. Turlington BS, Edwards WD. Quantitation of mast cells in 100normal and 92 diseased human hearts. Implications for interpretation of endomyocardial biopsy specimens. Am J Cardiovasc Pathol 1988; 2: 151-7.
192. Fairweather D, Frisancho-Kiss S, Gatewood S, et al. Mast cells andinnate cytokines are associated with susceptibility to autoimmune heart disease following coxsackievirus B3 infection. Autoimmunity 2004; 37: 131-45.
193. Kulka M, Alexopoulou L, Flavell RA, Metcalfe DD. Activation ofmast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol 2004; 114: 174-82.
194. Abraham SN, Thankavel K, Malaviya R. Mast cells as modulatorsof host defense in the lung. Front Biosci 1997; 2: d78-d87.
195. Gordon JR, Galli SJ. Release of both preformed and newlysynthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE- dependent biological responses. J Exp Med 1991; 174: 103-7.
196. Lane J, Neumann D, Lafond-Walker A, et al. Interleukin 1 ortumor necrosis factor can promote Coxsackie B3-induced myocarditis in resistant B10.A mice. J Exp Med 1992; 175: 1123-9.
197. Huber S. T cells in coxsackievirus induced myocarditis. ViralImmunol 2004; 17: 152-164.
198. Saligrama N, Noubade R, Case LK, et al. Combinatorial roles forhistamine H1-H2 and H3-H4 receptors in autoimmune inflammatory disease of the central nervous system. Eur J Immunol 2012; 42: 1536-46.
199. Jutel M, Akdis M, Akdis CA. Histamine, histamine receptors andtheir role in immune pathology. Clin Exp Allergy 2009; 39: 1786-1800.
200. Jutel M, Blaser K, Akdis CA. The role of histamine in regulation ofimmune responses. Chem Immunol Allergy 2006; 91: 174-87.
201. Jutel M, Klunker S, Akdis M, et al. Histamine upregulates Th1 anddownregulates Th2 responses due to different patterns of surface histamine 1 and 2 receptor expression. Int Arch Allergy Immunol 2001; 124: 190-2.
202. Jutel M, Watanabe T, Klunker S, et al. Histamine regulates T-celland antibody responses by differential expression of H1 and H2 receptors. Nature 2001; 413: 420-5.
203. Case LK, Moussawi M, Roberts B, et al. Histamine H(1) receptorsignaling regulates effector T cell responses and susceptibility to coxsackievirus B3-induced myocarditis. Cell Immunol 2012; 272: 269-74.
204. Anderson D, Carthy C, Wilson J, et al. Complement component 3interactions with coxsackievirus B3 capsid proteins: innate immunity and the rapid formation of splenic antiviral germinal centers. J Virol 1997; 71: 8841-5.
205. Mena I, Perry CM, Harkins S, et al. The role of B lymphocytes incoxsackievirus B3 infection. Am J Pathol 1999; 155: 1205-15.
206. Bergelson JM, Modlin JF, Wieland-Alter W, et al. Clinicalcoxsackievirus B isolates differ from laboratory strains in their interaction with two cell surface receptors. J Infect Dis 1997; 175: 697-700.
207. Ikeda F, Haraguchi Y, Jinno A, et al. Human complementcomponent C1q inhibits the infectivity of cell-free HTLV-I. J Immunol 1998; 161: 5712-9.
208. Ikeda K, Wakimoto H, Ichikawa T, et al. Complement depletionfacilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant. J Virol 2000; 74: 4765-75.
209. Flutter B, Gao B. MHC class I antigen presentation--recentlytrimmed and well presented. Cell Mol Immunol 2004; 1: 22-30.
210. Blum JS, Wearsch PA, Cresswell P. Pathways of antigenprocessing. Annu Rev Immunol 2013; 31: 443-73.
211. Iezzi G, Karjalainen K, Lanzavecchia A. The duration of antigenicstimulation determines the fate of naive and effector T cells. Immunity 1998; 8: 89-95.
212. Kinnear G, Jones ND, Wood KJ. Costimulation blockade: currentperspectives and implications for therapy. Transplantation 2013; 95: 527-35
213. Steinman RM. The dendritic cell system and its role inimmunogenicity. Annu Rev Immunol 1991; 9: 271-96.
214. Eriksson U, Ricci R, Hunziker L, et al. Dendritic cell-inducedautoimmune heart failure requires cooperation between adaptive and innate immunity. Nat Med 2003; 9: 1484-90.
215. Flynn K, Mullbacher A. The generation of memory antigen-specific cytotoxic T cell responses by CD28/CD80 interactions in the absence of antigen. Eur J Immunol 1997; 27: 456-62.
216. Romieu-Mourez R, Francois M, Boivin MN, et al. Regulation ofMHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-gamma, TGF-beta, and cell density. J Immunol 2007; 179: 1549-58.
217. Li W, Whaley CD, Mondino A, Mueller DL. Blocked signaltransduction to the ERK and JNK protein kinases in anergic CD4+ T cells. Science 1996; 271: 1272-6.
218. Sloan-Lancaster J, Shaw AS, Rothbard JB, Allen PM. Partial T cellsignaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Cell 1994; 79: 913-22.
219. Bendiksen S, Rekvig OP. Interleukin-2, but not interleukin-15, isrequired to terminate experimentally induced clonal T-cell anergy. Scand J Immunol 2004; 60: 64-73.
220. Ohkusu-Tsukada K, Tominaga N, Udono H, Yui K. Regulation ofthe maintenance of peripheral T-cell anergy by TAB1-mediated p38 alpha activation. Mol Cell Biol 2004; 24: 6957-66.
221. Dengjel J, Schoor O, Fischer R, et al. Autophagy promotes MHCclass II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci USA 2005; 102: 7922-7.
222. Marrack P, Ignatowicz L, Kappler JW, et al. Comparison ofpeptides bound to spleen and thymus class II. J Exp Med 1993; 178: 2173-83.
223. Rammensee HG, Friede T, Stevanoviic S. MHC ligands andpeptide motifs: first listing. Immunogenetics 1995; 41: 178-228.
224. Jacobson S, Sekaly RP, Jacobson CL, et al. HLA class II-restrictedpresentation of cytoplasmic measles virus antigens to cytotoxic T cells. J Virol 1989; 63: 1756-62.
225. Jaraquemada D, Marti M, Long EO. An endogenous processingpathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells. J Exp Med 1990; 172: 947-54.
226. Bronietzki AW, Schuster M, Schmitz I. Autophagy in T-celldevelopment, activation and differentiation. Immunol Cell Biol 2015; 93: 25-34.
227. Wang F, Muller S. Manipulating autophagic processes inautoimmune diseases: a special focus on modulating chaperone- mediated autophagy, an emerging therapeutic target. Front Immunol 2015; 6: 252.
228. Lee HK, Mattei LM, Steinberg BE, et al. In vivo requirement forAtg5 in antigen presentation by dendritic cells. Immunity 2010; 32: 227-39.
229. Cuervo AM, Macian F. Autophagy and the immune function inaging. Curr Opin Immunol 2014; 29: 97-104.
230. Sahu R, Kaushik S, Clement CC, et al. Microautophagy ofcytosolic proteins by late endosomes. Dev Cell 2011; 20: 131-9.
231. Domingo E, Holland J. RNA virus mutations and fitness forsurvival. Am Rev Microbiol 1997; 51: 151-78.
232. Domingo E, Martin V, Perales C, Escarmis C. Coxsackievirusesand quasispecies theory: evolution of enteroviruses. Curr Top Microbiol Immunol 2008; 323: 3-32.
233. Knowlton KU, Jeon ES, Berkley N, et al. A mutation in the puffregion of VP2 attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff variant of coxsackievirus B3. J Virol 1996; 70: 7811-8.
234. Coronado MJ, Brandt JE, Kim E, et al. Testosterone andinterleukin-1beta increase cardiac remodeling during coxsackievirus B3 myocarditis via serpin A 3n. Am J Physiol 2012; 302: H1726-36.
235. Onyimba JA, Coronado MJ, Garton AE, et al. The innate immuneresponse to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice. Biol Sex Differ 2011; 2: 2.
236. Afanasyeva M, Wang Y, Kaya Z, et al. Experimental autoimmunemyocarditis in A/J mice is an interleukin-4-dependent disease with a Th2 phenotype. Am J Pathol 2001; 159: 193-203.
237. Li HS, Ligons DL, Rose NR. Genetic complexity of autoimmunemyocarditis. Autoimmun Rev 2008; 7: 168-73.424
238. Herskowitz A, Beisel KW, Wolfgram LJ, Rose NR. CoxsackievirusB3 murine myocarditis: wide pathologic spectrum in genetically defined inbred strains. Hum Pathol 1985; 16: 671-3.
239. Herskowitz A, Wolfgram LJ, Rose NR, Beisel KW. CoxsackievirusB3 murine myocarditis: a pathologic spectrum of myocarditis in genetically defined inbred strains. J Am Coll Cardiol 1987; 9: 1311-9.
240. Wolfgram LJ, Beisel KW, Herskowitz A, Rose NR. Variations inthe susceptibility to Coxsackievirus B3-induced myocarditis among different strains of mice. J Immunol 1986; 136: 1846-52.
241. Herzum M, Huber S, Maisch B. Coxsackie B3 myocarditis:Genetic aspects of different immunopathogenic mechanisms in BALB/c and DBA/2 mice. Antigenic specificity of heart reactive antibodies in DBA/2 mice. In: Schultheiss H, Ed. New Concepts in Viral Heart Disease. Berlin: Springer-Verlag 1988; pp. 188-94.
242. Huber S, Lodge P. Coxsackievirus B3 myocarditis: identification ofdifferent mechanisms in DBA/2 and Balb/c mice. Am J Pathol 1986; 122: 284.
243. Herzum M, Huber SA, Weller R, et al. Treatment of experimentalmurine Coxsackie B3 myocarditis. Eur Heart J 1991; 12 (Suppl D): 200-2.
244. Woodruff J, Woodruff J. Involvement of T lymphocytes in thepathogenesis of coxsackievirus B3 heart disease. J Immunol 1974; 113: 1726-34.
245. Woodruff J. Lack of correlation between neutralizing antibodyproduction and suppression of coxsackievirus B-3 replication in target organs: evidence for involvement of mononuclear inflammatory cells in defense. J Immunol 1979; 123: 31-6.
246. Lutton C, Gauntt C. Ameliorating effect of IFN-B and anti-IFN-Bon coxsackievirus B3-induced myocarditis in mice. J Interferon Res 1985; 5: 137-46.
247. Althof N, Harkins S, Kemball CC, et al. In vivo ablation of type Iinterferon receptor from cardiomyocytes delays coxsackieviral clearance and accelerates myocardial disease. J Virol 2014; 88: 5087-99.
248. Kemball CC, Harkins S, Whitmire JK, et al. Coxsackievirus B3inhibits antigen presentation in vivo, exerting a profound and selective effect on the MHC class I pathway. PLoS Pathogens 2009; 5: e1000618.
249. Calabrese F, Carturan E, Chimenti C, et al. Overexpression oftumor necrosis factor (TNF)alpha and TNFalpha receptor I in human viral myocarditis: clinicopathologic correlations. Mod Pathol 2004; 17: 1108-18.
250. Rose NR, Hill SL. The pathogenesis of postinfectious myocarditis.Clin Immunol Immunopathol 1996; 80: S92-S9.
251. Tang Z, McGowan BS, Huber SA, et al. Gene expression profilingduring the transition to failure in TNF-alpha over-expressing mice demonstrates the development of autoimmune myocarditis. J Mol Cell Cardiol 2004; 36: 515-30.
252. Huber SA, Sartini D. Roles of tumor necrosis factor alpha (TNF-alpha) and the p55 TNF receptor in CD1d induction and coxsackievirus B3-induced myocarditis. J Virol 2005; 79: 2659-65.
253. Freeman G, Colston J, Zabalgoitia M, Chandrasekar B. Contractiledepression and expression of proinflammatory cytokines and iNOS in viral myocarditis. Am J Physiol 1998; 274: H249-H58.
254. Fairweather D, Frisancho-Kiss S, Yusung SA, et al. Interferon-gamma protects against chronic viral myocarditis by reducing mast cell degranulation, fibrosis, and the profibrotic cytokines transforming growth factor-beta 1, interleukin-1 beta, and interleukin-4 in the heart. Am J Pathol 2004; 165: 1883-94.
255. Abston ED, Coronado MJ, Bucek A, et al. Th2 regulation of viralmyocarditis in mice: different roles for TLR3 versus TRIF in progression to chronic disease. Clin Dev Immunol 2012; 2012: 129486.
256. Reetoo KN, Osman SA, Illavia SJ, et al. Quantitative analysis ofviral RNA kinetics in coxsackievirus B3-induced murine myocarditis: biphasic pattern of clearance following acute infection, with persistence of residual viral RNA throughout and beyond the inflammatory phase of disease. J Gen Virol 2000; 81: 2755-62.
257. Klingel K, Hohenadl C, Canu A, et al. Ongoing enterovirus-induced myocarditis is associated with persistant heart muscle infection: Quantitative analysis of virus replication, tissue damage and inflammation. Proc Natl Acad Sci USA 1992; 89: 314-8.
258. Zhang H, Li Y, McClean DR, et al. Detection of enterovirus capsidprotein VP1 in myocardium from cases of myocarditis or dilatedSally A. Hubercardiomyopathy by immunohistochemistry: further evidence of enterovirus persistence in myocytes. Med Microbiol Immunol 2004; 193: 109-14.
259. Gluck B, Schmidtke M, Merkle I, et al. Persistent expression ofcytokines in the chronic stage of CVB3-induced myocarditis in NMRI mice. J Mol Cell Cardiol 2001; 33: 1615-26.
260. Marcelletti JF, Katz DH. Antigen concentration determines helperT cell subset participation in IgE antibody responses. Cell Immunol 1992; 143: 405-19.
261. Horwitz M, Sarvetnick N. Viruses, host responses, andautoimmunity. Immunol Rev 1999; 169: 241-53.
262. Savino W. The thymus is a common target organ in infectiousdiseases. PLoS Pathogens 2006; 2: e62.
263. Brilot F, Geenen V, Hober D, Stoddart CA. Coxsackievirus B4infection of human fetal thymus cells. J Virol 2004; 78: 9854-61.
264. Shih FF, Mandik-Nayak L, Wipke BT, Allen PM. Massive thymicdeletion results in systemic autoimmunity through elimination of CD4+ CD25+ T regulatory cells. J Exp Med 2004; 199: 323-35.
265. Michaux H, Martens H, Jaidane H, et al. How does thymusinfection by coxsackievirus contribute to the pathogenesis of type 1 diabetes? Front Immunol 2015; 6: 338.
266. Theofilopoulos A. The basis for autoimmunity: Part I, mechanismsof aberrant self-recognition. Immunol Today 1995; 16: 90-8.
267. Pugliese A. Central and peripheral autoantigen presentation inimmune tolerance. Immunology 2004; 111: 138-46.
268. Caforio AL, Tona F, Bottaro S, et al. Clinical implications of anti-heart autoantibodies in myocarditis and dilated cardiomyopathy. Autoimmunity 2008; 41: 35-45.
269. Fujinami RS, Oldstone MB. Amino acid homology between theencephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 1985; 230: 1043-5.
270. Fujinami R, Oldstone M, Wroblewska Z, et al. Molecular mimicryin virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci USA 1983; 80: 2346-50.
271. Rose NR, Mackay IR. Molecular mimicry: a critical look atexemplary instances in human diseases. Cell Mol Life Sci 2000; 57: 542-51.
272. Schwimmbeck PL, Oldstone MB. Molecular mimicry betweenhuman leukocyte antigen B27 and Klebsiella. Consequences for spondyloarthropathies. Am J Med 1988; 85: 51-3.
273. Schwimmbeck PL, Oldstone MB. Klebsiella pneumoniae and HLAB27-associated diseases of Reiter's syndrome and ankylosing spondylitis. Curr Top Microbiol Immunol 1989; 145: 45-56.
274. Schwimmbeck PL, Dyrberg T, Drachman DB, Oldstone MB.Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus. J Clin Invest 1989; 84: 1174-80.
275. Hiemstra HS, Schloot NC, van Veelen PA, et al. Cytomegalovirusin autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase. Proc Natl Acad Sci USA 2001; 98: 3988-91.
276. Cunningham M, Hall N, Krisher K, Spanier A. A study of anti-group A streptococcal monoclonal antibodies crossreactive with myosin. J Immunol 1986; 136: 293.
277. Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995; 80: 695-705.
278. Ramos-Casals M, De Vita S, Tzioufas AG. Hepatitis C virus,Sjogren's syndrome and B-cell lymphoma: linking infection, autoimmunity and cancer. Autoimmunity Rev 2005; 4: 8-15.
279. Vreugdenhil GR, Batstra MR, Aanstoot HJ, et al. Analysis ofantibody responses against coxsackie virus B4 protein 2C and the diabetes autoantigen GAD(65). J Med Virol 1999; 59: 256-61.
280. Evavold BD, Sloan-Lancaster J, Wilson KJ, et al. Specific T cellrecognition of minimally homologous peptides: evidence for multiple endogenous ligands. Immunity 1995; 2: 655-63.
281. Wucherpfennig K, Strominger J. Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995; 80: 695-705.
282. Wucherpfennig KW, Sette A, Southwood S, et al. Structuralrequirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J Exp Med 1994; 179: 279-90
283. Benoist C, Mathis D. Autoimmunity provoked by infection: howgood is the case for T cell epitope mimicry? Nat Immunol 2001; 2: 797-801.
284. Stathopoulou EA, Routsias JG, Stea EA, et al. Cross-reactionbetween antibodies to the major epitope of Ro60 kD autoantigen and a homologous peptide of Coxsackie virus 2B protein. Clin Exp Immunol 2005; 141: 148-54.
285. Triantafyllopoulou A, Moutsopoulos HM. Autoimmunity andcoxsackievirus infection in primary Sjogren's syndrome. Ann N Y Acad Sci 2005; 1050: 389-96.
286. Triantafyllopoulou A, Tapinos N, Moutsopoulos HM. Evidence forcoxsackievirus infection in primary Sjogren's syndrome. Arthritis Rheum 2004; 50: 2897-902.
287. Youinou P, Pers JO, Saraux A, Pennec YL. Viruses contribute tothe development of Sjogren's syndrome. Clin Exp Immunol 2005; 141: 19-20.
288. Lonnrot M, Hyoty H, Knip M, et al. Antibody cross-reactivityinduced by the homologous regions in glutamic acid decarboxylase (GAD65) and 2C protein of coxsackievirus B4. Childhood Diabetes in Finland Study Group. Clin Exp Immunol 1996; 104: 398-405.
289. Maclaren NK, Alkinson MA. Insulin-dependent diabetes mellitus:the hypothesis of molecular mimicry between islet cell antigens and microorganisms. Mol Med Today 1997; 3: 76-83.
290. Gauntt C, Higdon A, Arizpe H, et al. Epitopes shared betweenCoxsackievirus B3 (CVB3) and normal heart tissue contribute to CVB3-induced murine myocarditis. Clin Immunol Immunopathol 1993; 68: 129-34.
291. Gauntt C, Winfey C, Wood H, et al. Anti-coxsackievirus group Bantibodies and inflammatory heart disease. In: Pandalai G, Ed. Recent Research Developments in Antimicrobial Agents and Chemotherapy. Trivandrum, India: Research Signpost 1996; pp. 257-70.
292. Huber SA, Cunningham MW. Streptococcal M protein peptide withsimilarity to myosin induces CD4+ T cell-dependent myocarditis in MRL/++ mice and induces partial tolerance against coxsakieviral myocarditis. J Immunol 1996; 156: 3528-34.
293. Root-Bernstein R, Vonck J, Podufaly A. Antigeniccomplementarity between coxsackie virus and streptococcus in the induction of rheumatic heart disease and autoimmune myocarditis. Autoimmunity 2009; 42: 1-16.
294. Massilamany C, Gangaplara A, Steffen D, Reddy J. Identificationof novel mimicry epitopes for cardiac myosin heavy chain-alpha that induce autoimmune myocarditis in A/J mice. Cell Immunol 2011; 271: 438-49.
295. Massilamany C, Huber SA, Cunningham MW, Reddy J. Relevanceof molecular mimicry in the mediation of infectious myocarditis. J Cardiovasc Trans Res 2014; 7: 165-171.
296. Kim BS, Lyman MA, Kang BS, et al. Pathogenesis of virus-induced immune-mediated demyelination. Immunol Res 2001; 24: 121-30.
297. Gangaplara A, Massilamany C, Brown DM, et al. CoxsackievirusB3 infection leads to the generation of cardiac myosin heavy chain- alpha-reactive CD4 T cells in A/J mice. Clin Immunol 2012; 144: 237-49.
298. Lanzavecchia A. How can cryptic epitopes trigger autoimmunity? JExp Med 1995; 181: 1945-8.
299. Sercarz E, Lehmann P, Ametani A, et al. Dominance and crypticityof T cell antigenic determinants. Ann Rev Immunol 1993; 11: 729-66.
300. Luo H, Zhang J, Dastvan F, et al. Ubiquitin-dependent proteolysisof cyclin D1 is associated with coxsackievirus-induced cell growth arrest. J Virol 2003; 77: 1-9.
301. Vidard L, Rock KL, Benacerraf B. Heterogeneity in antigenprocessing by different types of antigen-presenting cells. Effect of cell culture on antigen processing ability. J Immunol 1992; 149: 1905-11.
302. Gresser O, Weber E, Hellwig A, et al. Immunocompetentastrocytes and microglia display major differences in the processing of the invariant chain and in the expression of active cathepsin L and cathepsin S. Eur J Immunol 2001; 31: 1813-24.
303. Caporossi AP, Bruno G, Salemi S, et al. Autoimmune T-cellresponse to the CD4 molecule in HIV-infected patients. Viral Immunol 1998; 11: 9-17
304. Salemi S, Caporossi AP, Boffa L, et al. HIVgp120 activatesautoreactive CD4-specific T cell responses by unveiling of hidden CD4 peptides during processing. J Exp Med 1995; 181: 2253-7.
305. Simitsek PD, Campbell DG, Lanzavecchia A, et al. Modulation ofantigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants. J Exp Med 1995; 181: 1957-63.
306. Driessen C, Lennon-Dumenil AM, Ploegh HL. Individualcathepsins degrade immune complexes internalized by antigen- presenting cells via Fcgamma receptors. Eur J Immunol 2001; 31: 1592-601.
307. Speca S, Giusti I, Rieder F, Latella G. Cellular and molecularmechanisms of intestinal fibrosis. World J Gastroenterol 2012; 18: 3635-61.
308. Manner J. Does the subepicardial mesenchyme contributemyocardioblasts to the myocardium of the chick embryo heart? A quail-chick chimera study tracing the fate of the epicardial primordium. Anatomical Record 1999; 255: 212-26.
309. Gittenberger-de Groot AC, Winter EM, Bartelings MM, et al. Thearterial and cardiac epicardium in development, disease and repair. Differentiation. Res Biol Diversity 2012; 84: 41-53.
310. Kania G, Blyszczuk P, Valaperti A, et al. Prominin-1+/CD133+bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis. Cardiovasc Res 2008; 80: 236-45.
311. Zeisberg EM, Tarnavski O, Zeisberg M, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med 2007; 13: 952-61.
312. Ghosh AK, Nagpal V, Covington JW, et al. Molecular basis ofcardiac endothelial-to-mesenchymal transition (EndMT): differential expression of microRNAs during EndMT. Cell Signal 2012; 24: 1031-6.
313. Boutet A, Esteban MA, Maxwell PH, Nieto MA. Reactivation ofSnail genes in renal fibrosis and carcinomas: a process of reversed embryogenesis? Cell Cycle 2007; 6: 638-42.
314. Medici D, Potenta S, Kalluri R. Transforming growth factor-beta2promotes Snail-mediated endothelial-mesenchymal transition through convergence of Smad-dependent and Smad-independent signalling. Biochem J 2011; 437: 515-20.
315. Lee SW, Won JY, Kim WJ, et al. Snail as a potential targetmolecule in cardiac fibrosis: paracrine action of endothelial cells on fibroblasts through snail and CTGF axis. Mol Ther 2013; 21: 1767-77.
316. Lopez D, Niu G, Huber P, Carter WB. Tumor-induced upregulationof Twist, Snail, and Slug represses the activity of the human VE- cadherin promoter. Arch Biochem Biophys 2009; 482: 77-82.
317. Storci G, Sansone P, Mari S, et al. TNFalpha up-regulates SLUGvia the NF-kappaB/HIF1alpha axis, which imparts breast cancer cells with a stem cell-like phenotype. J Cell Physiol 2010; 225: 682-91.
318. Wu Y, Deng J, Rychahou PG, et al. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer cell 2009; 15: 416-28.
319. Sakaki-Yumoto M, Katsuno Y, Derynck R. TGF-beta familysignaling in stem cells. Biochim Biophys Acta 2013; 1830: 2280-96.
320. van Meeteren LA, ten Dijke P. Regulation of endothelial cellplasticity by TGF-beta. Cell Tissue Res 2012; 347: 177-86.
321. Goumans MJ, Valdimarsdottir G, Itoh S, et al. Balancing theactivation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J 2002; 21: 1743-53.
322. van Meeteren LA, Goumans MJ, ten Dijke P. TGF-beta receptorsignaling pathways in angiogenesis; emerging targets for anti- angiogenesis therapy. Curr Pharm Biotechnol 2011; 12: 2108-20.
323. Watabe T, Nishihara A, Mishima K, et al. TGF-beta receptorkinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells. J Cell Biol 2003; 163: 1303-11.
324. Birukova AA, Adyshev D, Gorshkov B, et al. ALK5 and Smad4are involved in TGF-beta1-induced pulmonary endothelial permeability. FEBS Lett 2005; 579: 4031-7.
325. Yoshimatsu Y, Watabe T. Roles of TGF-beta signals inendothelial-mesenchymal transition during cardiac fibrosis. Int J Inflam 2011; 2011: 724080.
326. Masszi A, Di Ciano C, Sirokmany G, et al. Central role for Rho inTGF-beta1-induced alpha-smooth muscle actin expression during epithelial-mesenchymal transition. Am J Physiol Renal Physiol 2003; 284: F911-F24.
327. Hall A. Rho GTPases and the control of cell behaviour. BiochemSoc Trans 2005; 33: 891-5.
328. Khokha R, Murthy A, Weiss A. Metalloproteinases and theirnatural inhibitors in inflammation and immunity. Nat Rev Immunol 2013; 13: 649-65.
329. Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases inlung: multiple, multifarious, and multifaceted. Physiol Rev 2007; 87: 69-98.
330. Ulasov I, Yi R, Guo D, et al. The emerging role of MMP14 in braintumorigenesis and future therapeutics. Biochim Biophys Acta 2014; 1846: 113-20.
331. Bumdelger B, Kokubo H, Kamata R, et al. Induction of Timp1 insmooth muscle cells during development of abdominal aortic aneurysms. Hiroshima J Med Sci 2013; 62: 63-7.
332. Westermann D, Savvatis K, Lindner D, et al. Reduced degradationof the chemokine MCP-3 by matrix metalloproteinase-2 exacerbates myocardial inflammation in experimental viral cardiomyopathy. Circulation 2011; 124: 2082-93.
333. Kania G, Blyszczuk P, Eriksson U. Mechanisms of cardiac fibrosisin inflammatory heart disease. Trend Cardiovasc Med 2009; 19: 247-52.
334. Tschope C, Miteva K, Schultheiss HP, Linthout SV. Mesenchymalstromal cells: a promising cell source for the treatment of inflammatory cardiomyopathy. Curr Pharm Des 2011; 17: 3295-307.
335. Hua JY, Zhang ZC, Jiang XH, et al. Relationship betweenendothelial-to-mesenchymal transition and cardiac fibrosis in acute viral myocarditis. Zhejiang Da Xue Xue Bao Yi Xue Ban 2012; 41: 298-304.
336. Kania G, Blyszczuk P, Stein S, et al. Heart-infiltrating prominin-1+/CD133+ progenitor cells represent the cellular source of transforming growth factor beta-mediated cardiac fibrosis in experimental autoimmune myocarditis. Circ Res 2009; 105: 462-70.
337. Lang C, Sauter M, Szalay G, et al. Connective tissue growth factor:a crucial cytokine-mediating cardiac fibrosis in ongoing enterovirus myocarditis. J Mol Med (Berl) 2008; 86: 49-60.
338. Xie Y, Liao J, Li M, et al. Impaired cardiac microvascularendothelial cells function induced by Coxsackievirus B3 infectionand its potential role in cardiac fibrosis. Virus Res 2012; 169: 188-94.
339. Sun B, Zhang Y. Overview of orchestration of CD4+ T cell subsetsin immune responses. Advances in experimental medicine and biology 2014; 841: 1-13.
340. Yang Z, Mu Z, Dabovic B, et al. Absence of integrin-mediatedTGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. J Cell Biol 2007; 176: 787-93.
341. Yoshida Y, Yoshimi R, Yoshii H, et al. The transcription factorIRF8 activates integrin-mediated TGF-beta signaling and promotes neuroinflammation. Immunity 2014; 40: 187-98.
342. Xu H, Zhu J, Smith S, et al. Notch-RBP-J signaling regulates thetranscription factor IRF8 to promote inflammatory macrophage polarization. Nat Immunol 2012; 13: 642-50.
343. Liu Q, Chen Y, Auger-Messier M, Molkentin JD. Interactionbetween NFkappaB and NFAT coordinates cardiac hypertrophy and pathological remodeling. Circ Res 2012; 110: 1077-86.
344. Herum KM, Lunde IG, Skrbic B, et al. Syndecan-4 signaling viaNFAT regulates extracellular matrix production and cardiac myofibroblast differentiation in response to mechanical stress. J Mol Cell Cardiol 2013; 54: 73-81.
345. Yang J, Zeini M, Lin CY, et al. Epicardial calcineurin-NFATsignals through Smad2 to direct coronary smooth muscle cell and arterial wall development. Cardiovasc Res 2014; 101: 120-9.
346. Sengupta S, Jana S, Bhattacharyya A. TGF-beta-Smad2 dependentactivation of CDC 25A plays an important role in cell proliferation through NFAT activation in metastatic breast cancer cells. Cell Signal 2014; 26: 240-52.
347. Chang CP, Neilson JR, Bayle JH, et al. A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Cell 2004; 118: 649-63.
348. Irvin SC, Zurney J, Ooms LS, et al. A single-amino-acidpolymorphism in reovirus protein mu2 determines repression of interferon signaling and modulates myocarditis. J Virol 2012; 86: 2302-11.
349. McCarthy MK, Procario MC, Twisselmann N, et al. Proinflam-matory effects of interferon gamma in mouse adenovirus 1 myocarditis. J Virol 2015; 89: 468-79